Action Points

Note that this large, population-based, British study suggested an association between increasing BMI and a wide variety of cancers.

Be aware that physicians may be more likely to note high BMI among individuals with other conditions (such as diabetes) that may predispose to malignancy.

Increasing body size had significant associations with 10 common types of cancer, a study involving more than 5 million people showed.

Overall, body mass index (BMI) had linear associations with the risk of uterine, gallbladder, kidney, cervical, and thyroid cancer, as well as leukemia. The magnitude of excess risk associated with increasing BMI ranged from 9% to 62%.

BMI had lesser but still positive associations with liver, colon, ovarian, and postmenopausal breast cancer, British investigators reported online in The Lancet.

"Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight," Krishnan Bhaskaran, MSc, PhD, of the London School of Hygiene and Tropical Medicine, and co-authors concluded. "We estimated that a 1 kg (2.2 lb) per-meter-squared population-wide increase in BMI would result in 3,790 additional annual U.K. patients developing one of the 10 cancers positively associated with BMI."

Heterogeneous associations between BMI and cancer risk suggest different mechanisms are involved in BMI's contribution to carcinogenesis at different sites, they added.

The worldwide epidemic of obesity has added a sense of urgency to research aimed at improved understanding of the effects of adiposity on health outcomes, including cancer. A large volume of data, primarily from observational studies and meta-analyses, has shown significant associations between BMI and several types of cancer, but many of the studies had inadequate statistical power and other limitations that precluded definitive conclusions and extrapolation, the authors noted in their introduction.

To increase the amount of broadly applicable information, Bhaskaran and co-authors analyzed data from the Clinical Practice Research Datalink (CPRD), which houses primary care records covering about 9% of the British population. The database includes information about diagnoses, prescriptions, tests, referrals to specialists, hospital admissions, and secondary diagnoses in specialty care. Additionally, participating general practitioners record information about lifestyle factors and anthropometric parameters.

CPRD data collection began in 1987, and Bhaskaran and colleagues analyzed data captured through July 2012. The primary outcome was the number of cases of the 21 most common cancers, a list that encompasses 90% of all cancers diagnosed in England each year. Additionally, the investigators included gallbladder cancer because of evidence suggesting an association with BMI.

The analysis included 5.24 million patients, who developed a total of 201,504 cancers during a mean follow-up of 7.5 years. The total cancer volume included 166,955 cancers prespecified for the analysis.

In all cases, BMI values used in the study were identified after patients had been enrolled in a CPRD practice for at least 12 months. For statistical analysis, investigators limited BMI exposure to 12 months to avoid confounding by reverse causality (effects of undiagnosed cancer on BMI).

The results showed that every 5.5 kg (~11 lb)/m2 increase in BMI was associated with increases in the hazard for the following cancers:

The authors also found inverse associations between BMI and prostate cancer (HR 0.96, 0.93-0.99) and premenopausal breast cancer (HR 0.89, 95% CI 0.86-0.92). Nonsmokers had the same hazard for both of the cancers. Nonsmokers did not have a lower risk of lung cancer (0.99, 95% CI 0.93-1.05) or oral cavity cancer (HR 1.07, 95% CI 0.91-1.26).

In an accompanying commentary, Peter T. Campbell, PhD, of the American Cancer Society, characterized obesity as "a certain and avoidable cause of cancer."

"We have sufficient evidence that obesity is an important cause of unnecessary suffering and death from many forms of cancer, in addition to the well recognized increased risks of mortality and morbidity from many other causes," Campbell wrote. "More research is not needed to justify, or even demand, policy changes aimed at curbing overweight and obesity.

"Research strategies that identify population-wide or community-based interventions and policies that effectively reduce overweight and obesity should be particularly encouraged and supported," Campbell added. "Moreover, we need a political environment, and politicians with sufficient courage, to implement such policies effectively."

By documenting associations with almost two dozen cancers, the study builds a strong case that "obesity is one of the most important risk factors for cancer, second to tobacco," said Paolo Boffetta, MD, of Mount Sinai Medical Center in New York City.

"After tobacco, in the U.S. and Europe, obesity is probably the single most important cause of cancer that can be prevented," Boffetta told MedPage Today. "This study provides the strongest evidence for an association with larger number of cancers, so for the importance of preventing cancer, the obesity rate -- the epidemic -- is even more important."

The observation that obesity and overweight had associations with 17 of 22 cancers suggests an even greater problem than previously recognized, said Katherine Tkaczuk, MD, of the University of Maryland Medical Center in Baltimore.

Beyond the associations with cancer, the study showed that even relatively modest increases in weight raise a person's risk of developing cancer, according to Stephen Freedland, MD, of Duke University. However, several key questions remain unanswered, such as how excess weight increases cancer risk and whether weight loss reduces the risk of cancer.

"The question I want to know is 'why,'" said Freedland. "Secondly, what can we do about it?"

The study was supported by the National Institute for Health Research, the Wellcome Trust, and the Medical Research Council.

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